The impact of phosphate lowering agents on clinical and laboratory outcomes in chronic kidney disease patients: a systematic review and meta-analysis of randomized controlled trials

J Nephrol. 2022 Mar;35(2):473-491. doi: 10.1007/s40620-021-01065-3. Epub 2021 Jun 1.


Background: Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients.

Method: A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables.

Results: This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed.

Conclusions: In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.

Keywords: Cardiovascular outcomes; Chronic kidney disease; Hyperphosphatemia; Mortality; Phosphate lowering agents.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Humans
  • Hyperphosphatemia* / drug therapy
  • Hyperphosphatemia* / etiology
  • Phosphates
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / diagnosis
  • Renal Insufficiency, Chronic* / drug therapy
  • Sevelamer / therapeutic use


  • Phosphates
  • Sevelamer